Download cell-membrane-5-11-16

Cell Organelles &
Cell Membrane
Dr. Ketki
Assistant Professor
Department of Biochemistry
Heritage IMS, Varanasi
• "Education is the best friend.
An educated person is
respected everywhere.
Education beats the beauty
and the youth."
Chanakya quotes (Indian politician, strategist and
writer, 350 BC-275BC)
Content
Cell organelles
1) Mitochondria & its clinical applications
2) Lysosomes & its clinical applications
3) Peroxisomes & its clinical applications
Plasma Membrane
1) Lipid Bilayer/Micelle/Liposome
2) Fluid Mosaic Model
3) Membrane proteins
4) Specialized membrane structures
Mitochondria
 Spherical, oval/ rod like bodies
 0.5 µm in diameter & upto 7µm in length
RBC doesn’t contain mitochondria
The tail of spermatozoa is fully packed with it
“Power house of the cell”
Mitochondria have 2 membranes
1) Outer mitochondrial Membrane
2) Inner mitochondrial Membrane
Location of enzymes in Mitochondria
Location
Enzymes
Mitochondrial,outer membrane
Monoamine oxidase
Acyl coA synthetase
Phospholipase A2
In between outer and inner
membrane
Adenylate Kinase
Creatine Kinase
Inner membrane,outer surface
Glycerol 3 phosphate dehydrogenase
Inner membrane,inner surface
Succinate dehydrogenase
Enzymes of respiratory chain
Soluble matrix
Enzymes of citric acid cycle,
β oxidation of fatty acid, Urea cycle &
heme synthesis
 Mitochondria contains specific DNA
 Mitochondrial ribosomes are different from cellular
ribosomes.
i) Integral inner membrane proteins are synthesized by
mitochondrial ribosomes.
ii) Outer membrane protein synthesis ,under control of
cellular ribosomes
Mitochondria- Clinical aspects
 Mitochondrial DNA can be damaged by free radicals
 Age related degenerative disorders such as Parkinson’s
diseases & cardiomyopathy are related to mitochondrial
disorders
 Defects in mitochondrial DNA leads to – Mitochondrial
myopathies also known as Oxidative Phosphorylation
diseases.
Eg: Leber’s hereditary optic neuropathy
Myoclonic epilepsy ragged red fibre disease etc.
Lysosomes
 Discovered by Rene de Duve
 Tiny organelles containing enzymes(bag of enzymes)
 Foreign particles are progressively digested inside these
vacuoles.
 Completely hydrolysed products are utilised by the cell.
 As long as the lysosomal membrane is intact , the
encapsulated enzymes can act only locally.
 But when the membrane is disrupted, the released
enzymes can hydrolyse external substrates – tissue
damage.
Lysosomal enzymes
Examples
Polysaccharide hydrolyzing
enzymes
Alpha-glucosidase,
alpha-fucosidase,betagalactosidase, aryl sulfatase
Protein hydrolyzing enzymes
Cathepsins, collagenase,
elastase
Nucleic acid hydrolyzing enzymes
Ribonuclease,
deoxyribonuclease
Lipid hydrolyzing enzymes
Fatty acyl esterase,
phospholipases
Clinical applications of lysosomes
1) In Gout
2) Postmortem autolysis
3) Cathepsins in tumor metastasis
4) Silicosis
5) Inclusion cell disease(I -cell disease)
Peroxisomes
 Granular Matrix
 0.3-1.5 mm in diameter
 Contain peroxidase & catalase
 Prominent in leukocytes & platelets
 Peroxidation of PUFA lead to hydroperoxide formation.
 Free radicals damage molecules,cell membranes,tissues
& genes
 Catalase & peroxidase: enzymes present in peroxisomes,
will destroy unwanted peroxides & other free radicals
Clinical applications of Peroxisomes
 Adrenoleukodystrophy
(Brown-Schilder’s disease)
 Zellweger syndrome
 Primary hyperoxaluria
Metabolic functions of subcellular
organelles
Nucleus
DNA replication,transcription
Endoplasmic Reticulum
Biosynthesis of proteins,glycoproteins,
lipoproteins,drug metabolism,ethanol
oxidation,synthesis of cholesterol(partial)
Golgi appartus
Maturation of synthesized proteins
Lysosome
Degradation of proteins,carbohydrates, lipids &
nucleotides
Mitochondria
ETC,ATP generation, TCA cycle, β oxidation of FA,
Urea synthesis(part),
heme synthesis(part), gluconeogenesis(part),
pyrimidine synthesis(part)
Cytosol
Protein synthesis,glycolysis,glycogen
metabolism,HMP shunt pathway,
Transamination,fatty acid synthesis,
cholesterol synthesis,heme synthesis(part),
urea synthesis(part),
pyrimidine synthesis(part),purine synthesis
Plasma Membrane
Separates cell from external environment
Permeability property
Cellular metabolism
Ectoenzymes
Membrane made up of
Lipids, proteins, small amount of carbohydrates
Mainly Phospholipids, cholesterol, glycoproteins
& glycolipids
Membrane lipids are Amphipathic
Fig: shows diagrammatic representation of Membrane Lipids
Membrane lipids form bilayers
 Polar head
(extracellular side/outer leaflet/external layer
choline containing phospholipids)
 Nonpolar tail
(cytoplasmic side/inner leaflet/inner layer
ethanolamine & serine containing phospholipids )
Fig: shows diagram of section of Lipid Bilayer
Phospholipids form Micelles
 Hydrophobic region shielded from water
 Hydrophilic region immersed in aqueous
environment
Artificial Membrane Model
Membrane Function
 Mixture of natural or synthetic phospholipids are treated to
induce formation of spherical vesicle in which lipids form a
bilayer.
 Such vesicles are surrounded by lipid bilayer with an aqeous
interior, are termed liposomes
 Such liposomes can be made to entrap drugs and isolated
genes.
 Liposomes are useful to target specific tissue or tumors.
 It may prove useful in gene therapy
Fluid Mosaic Model
Lipid bilayer- Davson & Danielle
Structure of biomembrane described as fluid
mosaic model by Singer & Nicolson
Each leaflet is 25 A⁰ thick
Head portion 10 A⁰ , Tail portion 15 A⁰,
Total thickness 50-80 A⁰
Lipid bilayer shows free lateral movement of it’s
components, hence fluidic in nature
Inside-outside asymmetry of phospholipids,
flip-flop movement is limited.
Fluidity of membrane depends upon
lipid composition of membrane
In a lipid bilayer, hydrophobic chain of FA is highly ordered
to form stiff structure
As temperature ↑,Hydrophobic side chains undergo transition from
ordered to disordered state
Temperature at which, this change takes place is called as, Transition
Temperature (Tm)
Longer & more saturated FA side chains interact more strongly with
each other
Leads to higher value of Tm, that is, higher temperature is required to
increase fluidity of lipid bilayer
In other words,Due to kink in the tail, Unsaturated FAs ↓ compactness
of side chains packing (↑ Fluidity)
Cholesterol acts as a buffer to modify
the fluidity of membrane
At temperature below Tm
Cholesterol ↑ Fluidity, Since it interferes
with interaction of hydrocarbon tails of FA
At temperature above Tm
Cholesterol ↓ Fluidity, Since it is more rigid
than hydrocarbon tails of FA
Fluidity of membrane is maintained by
1)
2)
3)

Length of hydrocarbon chain
Degree of unsaturation
Nature of polar head groups
Nature of FA & cholesterol varies depending
upon diet:
diet rich in PUFA: ↑ fluidity
 Physiological state also affect fluidity
↑ ROS/free radicals: ↓ fluidity
Membrane contain integral &
peripheral proteins
Fig: shows Fluid Mosaic Model of Membrane Structure
Integral proteins
They interact extensively with phospholipids
Span the lipid bilayer as a bundle of
transmembrane segments
Globular, amphipathic
Consists of two hydrophilic ends & intervening
hydrophobic region, which traverses the
hydrophobic core of lipid bilayer
Peripheral Proteins
Do not interact directly with hydrophobic core
of lipid bilayer
Bound to hydrophilic regions of specific
integral proteins
Eg:
Ankyrin: It’s a peripheral protein bound to
integral protein band 3 of RBC membrane
Questions?
1) How many biologically important molecules
are lipid soluble, and therefore can readily
enter cell?
1) How are the transmembrane concentration
of non lipid soluble molecules maintained?
Specialized features of plasma membrane
1) Lipid Rafts
2) Caveolae
3) Tight Junctions
4) Gap Junctions
Lipid Rafts
 Micro domain
Specialized areas of outer leaflet of lipid bilayer
Rich in cholesterol, sphingolipids, proteins
Involved in signal transduction (endocytosis,G
protein signaling & binding of viral pathogens)
Caveolae
Flask like indentations on area of lipid rafts
Contain protein caveolin-1,occurs as a dimer
Involved in signal transduction through
Insulin receptors
G proteins
Tight Junctions
Found in surface membrane
Located below apical surface of epithelial cells
Prevent diffusion of macromolecules between cells
Composed of proteins like, occludin, claudins,
junction adhesion molecule
• When two cells are in close approximation with
each other, instead of 4 layers, 3 layers of plasma
membranes are seen.
• This allows small molecules to pass through
narrow hydrophilic pores.
• So, some short of communication does exist b/w
cells
• Absence of this tight junction is implicated in
loss of contact inhibition in cancer cells
Gap Junctions
Intracellular channels
Function: To ensure a supply of nutrients to
cells of organ that are not in direct contact
with blood supply
Formed from protein called connexin
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